A retrospective review of changes and challenges in the use of antiseizure medicines in Dravet syndrome in Norway

Abstract

Objective Dravet syndrome is a developmental and epileptic encephalopathy characterized by severe and drug‐resistant seizures in early childhood, followed by developmental delay. The purpose of this study was to investigate aspects of pharmacological treatment of Norwegian patients with Dravet syndrome, focusing on the use of antiseizure medicines (ASMs) and identifying treatment challenges. Methods Patients were identified through medical registries at the National Center for Epilepsy in Norway and National Center for Rare Epilepsy Related Disorders during 2008‐2018. Additional clinical data were obtained from medical records and laboratory request forms. Results We identified 53 patients with Dravet syndrome, 30/23 males/females, aged 2‐50 years. The majority of patients with known seizure frequency experienced frequent seizures, 80% (n = 35/44). Only two patients were seizure‐free. Valproate (n = 48), clobazam (n = 45), levetiracetam (n = 30), and stiripentol (n = 38) were most commonly used, previous or current use. More than one‐third (n = 20) had tried sodium channel blockers (including lamotrigine), but these drugs were used less during the last decade. Polytherapy was common, 81% (n = 43) used two or more ASMs, and eight of these patients used 4‐5 drugs (15%). Several challenges were identified: high seizure frequency, comorbidities, treatment changes with a wide range of ASMs, common use of oral gastro‐tubes, extensive polypharmacy, and drug interactions. Significance The use of ASMs has changed over the last decade, in accordance with updated international recommendations. Various treatment challenges were identified. This vulnerable group of patients needs close follow‐up for an optimal treatment outcome.

Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: Analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome

“…In addition to frequent seizures in children and young adults with DS that may be associated with deficits in cognition, treatment with antiseizure medications (ASMs), which are often prescribed to reduce seizures, may further jeopardize cognition [22,[29][30][31], possibly mediated, at least in part, by their effects on EF [32]. Individuals with DS almost always require polytherapy [33], which significantly increases the likelihood of adverse cogni-tive drug effects [30,32,34,35].…”

“…In addition to frequent seizures in children and young adults with DS that may be associated with deficits in cognition, treatment with antiseizure medications (ASMs), which are often prescribed to reduce seizures, may further jeopardize cognition [22,[29][30][31], possibly mediated, at least in part, by their effects on EF [32]. Individuals with DS almost always require polytherapy [33], which significantly increases the likelihood of adverse cogni-tive drug effects [30,32,34,35]. Children and young adults with DS represent a particularly vulnerable population because multi-ASM combinations can have negative additive effects on cognition [29,31], especially if seizures are poorly controlled, during their most developmentally sensitive time period [22,23].…”

Dravet Syndrome—The Polish Family’s Perspective Study

“…Heger et al [ 26 ] in their study on the Norwegian population of 55 patients with DS also noted the problem of polytherapy and the resulting drug–drug interactions and indicated the three most commonly used drugs (i.e., valproic acid, clobazam and stiripentol), which could influence each other’s pharmacokinetics. Stiripentol is a potent inhibitor of hepatic enzymes and can displace valproic acid and clobazam from their protein binding sites, which results in increased drug concentrations in the blood and adverse effects such as ataxia or hair loss.…”

Genetics and clinical correlation of Dravet syndrome and its mimics – experience of a tertiary center in Taiwan

“…Stiripentol and cannabidiol have recently been introduced to treat DS. 37,38 Seven cases in our SCN1A group were treated with stiripentol. Among them, 3 patients achieved seizure freedom and 3 patients had a 50% reduction in seizures.…”